Axon Initial Segment Morphology Across Typical Cortical Development and in Mouse Models of Neurodevelopmental Disorders with a High Incidence of Epilepsy

Neurodevelopmental disorders (NDDs) are commonly associated with a high incidence of epileptic seizures which result from excessive firing of neurons. The axon initial segment (AIS) is a neuronal compartment essential for the control of activity patterns of neurons. The AIS undergoes important modifications during development, but the molecular mechanisms that affect the development, morphology, and protein composition of the AIS are still not well understood. We examined AIS morphology of medial prefrontal cortex (mPFC) pyramidal neurons in wildtype mice across development and in two mouse models of NDDs. Results indicate restructurings at the AIS during typical development, some of which are altered in mice models of NNDs where the AIS is shorter and highly disorganized when compared to wildtype mice. The observed morphological changes at the AIS in mice models of NDDs may impact neuronal cell firing or function. Furthering research on the development of the AIS compartment is fundamental to increasing our understanding of how this structure influences typical and atypical neurodevelopment. Particularly, increasing our knowledge of the development of the AIS in health and pathology may lead to new therapies for NDDs and epilepsy